Targeting the neuro-immune axis: immunological mechanisms and therapeutic strategies in male sexual dysfunction

Male sexual dysfunction (MSD) is a multifactorial condition in which traditional models focusing on vascular, endocrine, and psychogenic factors are insufficient. Emerging evidence highlights dysregulated crosstalk between the nervous and immune systems-the neuroimmune axis-as a potential unifying pathological substrate. This review synthesizes fragmented yet compelling evidence linking neural injury, chronic inflammation (both systemic and neurogenic), and immune dysregulation to the pathogenesis of MSD. We propose a novel integrative framework in which disruption of the neuro-immune axis serves as a convergent pathway for diverse etiologies, ranging from diabetic neuropathy to chronic pelvic pain. Central to this framework is the concept that immune-mediated processes exacerbate neural and vascular damage, creating a self-perpetuating cycle of dysfunction. Building on this mechanistic perspective, we explore the translational potential of neurosurgical and neuromodulatory strategies-such as sacral neuromodulation and vagus nerve stimulation-to restore neuroimmune homeostasis. Although direct clinical evidence in MSD remains limited, insights from related fields, including chronic pain and autoimmune disorders, provide a strong rationale for further investigation. This review aims to bridge mechanistic insights with therapeutic innovation, charting a course for future research into precision neuromodulation as a promising frontier for refractory MSD.